Plasma homocysteine and thiol compound fractions after oral administration of N-acetylcysteine

et al. 2009

J Nutr Sci Vitaminol

Summary Experiments were conducted to clarify the relationship between dietary protein level and plasma homocysteine concentration in rats. Male Wistar rats were fed diets differing in casein level from 5 to 50% for 14 d (Expt. 1). Plasma total homocysteine concentration was positively correlated with dietary casein level in the range of 5 to 10% but inversely correlated with dietary casein level in the range of 10 to 50%. Hepatic cystathionine ␤ -synthase (CBS) and betaine-homocysteine S -methyltransferase (BHMT) activities and renal CBS activity increased in response to dietary casein level in the range of 10 to 50%, whereas hepatic serine and betaine concentrations decreased with increasing dietary casein levels. When rats were fed the 10% casein diet or 10% casein ϩ 17.2% amino acid mixture diet for 14 d, plasma homocysteine concentration was significantly lower in rats fed the amino acid mixture-added diet than in rats fed the 10% casein diet (Expt. 2), indicating that the hypohomocysteinemic effect of high casein diets was elicited by amino acids, not by casein contaminants. The degree of increase in plasma homocysteine concentration caused by dietary supplementation with 0.75% L -methionine was significantly lower in rats fed the 40% casein diet than in rats fed the 10% casein diet (Expt. 3). These results indicate that high casein diets do not increase but rather decrease plasma homocysteine concentration and cause resistance to hyperhomocysteinemic treatment, and suggest that such effects of high casein diets are mediated at least by increased activities of CBS and BHMT. Key Words dietary casein level, homocysteine, methionine, cystathionine ␤ -synthase, betaine-homocysteine S -methyltransferase Homocysteine is one of the intermediates of methionine metabolism. A number of studies have suggested that an elevated plasma homocysteine concentration might be an independent risk factor for cardiovascular disease ( 1 -3 ). It has been shown that plasma homocysteine concentration is affected by several factors such as genetics, physiology, lifestyle, nutrition, clinical factors, and drugs ( 1 -3 ). Genetic factors and nutritional conditions are thought to have a greater influence on plasma homocysteine concentration. For instance, deficiencies of the vitamins such as folate, vitamin B-6, and vitamin B-12 increase plasma homocysteine concentration, because folate and vitamin B-12 are involved in the remethylation of homocysteine and vitamin B-6 is involved in the formation of cystathionine.Recently attention has also been focused on the effect of dietary proteins on plasma homocysteine concentration, since the intake of methionine, the sole precursor of homocysteine, is usually associated with the amount and type of dietary proteins ingested. In humans, it has been shown that a single ingestion of a high protein meal increased postprandial plasma homocysteine concentration ( 4 , 5 ), although the effect of the high protein meal was smaller than that of an equivalent amount of free methionine ( 5 ). In contrast,...

Section: Discussionsupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

High Casein Diet Decreases Plasma Homocysteine Concentration in Rats

Ohuchi

Matsumoto

et al. 2009

J Nutr Sci Vitaminol

“…3,19) In contrast, dietary addition of cysteine did not decrease, but rather increased, the plasma homocysteine concentration in the present study. The reason for the discrepancy between the results of previous studies and the results of this one appears at least in part to be different experimental conditions, e.g., the addition level and administration method of methionine and cysteine.…”

Section: )contrasting

confidence: 52%

“…Cysteine competes with homocysteine for transporters in several tissues 18) and for the homocysteine-binding site of plasma albumin. 19) Thus, the possibility that the increase in the plasma cysteine concentration is partly associated with the effects of glycine, serine, histidine, and arginine cannot be excluded, although the causal relationship is still unclear.…”

Section: )mentioning

confidence: 99%

Effects of Various Amino Acids on Methionine-Induced Hyperhomocysteinemia in Rats

Fukada

Bioscience, Biotechnology, and Biochemistry

Sugiyama

2008

Rats were fed diets supplemented with 1% L-methionine with and without 2.5% various amino acids for 7 d to determine what amino acids other than glycine, serine, and cystine can suppress methionine-induced hyperhomocysteinemia. L-Glutamic acid, L-histidine, and L-arginine significantly suppressed methionineinduced enhancement of plasma homocysteine concentrations, but the mechanisms underlying the effect of these amino acids are thought not to be identical.

“…In humans, about 75% of plasma homocysteine is bound to protein through disulfide bonds with cysteine residues of plasma proteins, especially albumin, and the remainder exists mainly in the forms of low-molecular-weight disulfides such as homocystine and homocysteine-cysteine (34). Hultberg et al (15) demonstrated that the plasma total homocysteine concentration in healthy humans was decreased after single oral administration of NAC, whereas non-protein-bound homocysteine concentration was increased. Based on these results, they postulated that administration of NAC (or cysteine) might displace homocysteine from its protein-binding site by disulfide exchange reaction and lead to the formation of mixed low-molecular-weight cysteine and NAC disulfides with high rate of renal clearance and an increased metabolic bioavailability, thereby eliminating homocysteine from plasma.…”

Section: Discussionmentioning

confidence: 99%

Hypohomocysteinemic Effect of Cysteine Is Associated with Increased Plasma Cysteine Concentration in Rats Fed Diets Low in Protein and Methionine Levels

Kawakami

Ohuchi

et al. 2009

J Nutr Sci Vitaminol

Summary Rats were fed diets with and without 0.5% L -cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C ϩ 0.65% methionine or 25C ϩ 0.4% guanidinoacetic acid. Hepatic S -adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine ␤ -synthase and betaine-homocysteine S -methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine. Key Words hypohomocysteinemic effect, cysteine, homocysteine, low protein diet, low methionine diet Homocysteine is an intermediate in the metabolism of methionine (Fig. 1) ( 1 ), but a number of studies have suggested that an elevated plasma homocysteine concentration is an independent risk factor for cardiovascular disease ( 2 -4 ). It is thought that elevated plasma homocysteine concentrations cause arterial damage by several mechanisms, e.g., endothelial cell injury, platelet activation, and increased oxidizability of low-density lipoproteins ( 4 ). In humans, the normal range of plasma homocysteine concentration is 5 to 15 M , and a 5-M increase in the concentration of this amino acid is associated with a 60-80% increased risk of coronary heart disease ( 3 ). The plasma homocysteine concentration is affected by various factors, such as nutritional, physiological, hormonal, pharmacological, lifestyle, disease, and genetic factors ( 2 -4 ). Of these factors, genetic and nutritional factors are thought to have a greater influence on plasma homocysteine concentration. Many studies have been conducted in humans to investigate the effect of dietary treatments on plasma homocysteine concentration. However, studie...